Superoxide Mediated Oxidation of PTEN Correlates with the Rapid Phosphorylation of Akt Induced by Fetal Bovine Serum in Serum Deprived Mouse Embryonic Fibroblast

摘要

In this report, we demonstrate that in serum deprived mouse embryonic fibroblasts (MEFs) an increase in intracellular superoxide (O_2) either through pharmacological or molecular inhibition of CuZn/SOD, mimics growth factor-mediated phosphorylation of Akt. Oxidation of the phosphatase PTEN is shown to be the mechanism involved in the phosphorylation of Akt by O_2~-Moreover, exposure of serum deprived MEFs to serum leads to a rapid and strong activation of Akt that is dependent on the production of O_2 and correlates with the oxidation of PTEN. These results support O_2~- as a physiologically relevant second messenger for Akt phosphorylation through inhibition of PTEN and offer a mechanistic explanation for the mitogenic and pro-survival activities of O_2~-.